1,090 research outputs found
CRF(1) receptor antagonists attenuate escalated cocaine self-administration in rats
RATIONALE: Previous work suggests a role for stress-related corticotropin-releasing factor (CRF) systems in cocaine dependence. However, the involvement of activation of CRF(1) receptors in rats self-administering cocaine with extended access is unknown. OBJECTIVE: The current study examined whether CRF(1) receptor antagonist administration alters cocaine self-administration in animals given extended access. MATERIALS AND METHODS: Wistar rats (n = 32) acquired cocaine self-administration (0.66 mg/kg per infusion) in 1 h sessions for up to 11 days. Rats then were assigned to receive either daily short (1 h, ShA) or long (6 h, LgA) access to cocaine self-administration (n = 7-9 per group). Following escalation of intake, animals received one of two selective CRF(1) antagonists: antalarmin (6.3-25 mg/kg, i.p.) or N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5a]pyrimidin-7-amine (MPZP; 3.6-27.5 mg/kg, s.c.). RESULTS: By day 11 of the escalation period, LgA rats increased their cocaine intake, reaching an intake level of 15.1 mg/kg, compared to 11.1 mg/kg in ShA rats, during the first hour of sessions. Antalarmin reduced cocaine self-administration at the highest dose selectively in the LgA group but not the ShA group. MPZP reduced cocaine intake both in LgA and ShA rats. However, MPZP did so at a lower dose in LgA rats than in ShA rats. Within the LgA group, MPZP decreased cocaine intake in the first 10 min (loading phase) as well as in the latter session intake (maintenance phase). CONCLUSION: The data suggest that hypersensitivity of the CRF system occurs with extended access to cocaine self-administration and that this altered CRF system may contribute to the increased motivation to self-administer cocaine that develops during psychostimulant dependence
Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferase in a cross-sectional study
Abstract Introduction A deletion polymorphism in glutathione S-transferase Mu-1 (GSTM1-null) has previously been implicated to play a role in rheumatoid arthritis (RA) risk and progression, although no prior investigations have examined its associations with anticitrullinated protein antibody (ACPA) positivity. The purpose of this study was to examine the associations of GSTM1-null with ACPA positivity in RA and to assess for evidence of interaction between GSTM1 and HLA-DRB1 shared epitope (SE). Methods Associations of GSTM1-null with ACPA positivity were examined separately in two RA cohorts, the Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 703) and the Study of New-Onset RA (SONORA; n = 610). Interactions were examined by calculating an attributable proportion (AP) due to interaction. Results A majority of patients in the VARA registry (76%) and SONORA (69%) were positive for ACPA with a similar frequency of GSTM1-null (53% and 52%, respectively) and HLA-DRB1 SE positivity (76% and 71%, respectively). The parameter of patients who had ever smoked was more common in the VARA registry (80%) than in SONORA (65%). GSTM1-null was significantly associated with ACPA positivity in the VARA registry (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.02 to 2.05), but not in SONORA (OR, 1.00; 95% CI, 0.71 to 1.42). There were significant additive interactions between GSTM1 and HLA-DRB1 SE in the VARA registry (AP, 0.49; 95% CI, 0.21 to 0.77; P < 0.001) in ACPA positivity, an interaction replicated in SONORA (AP, 0.38; 95% CI, 0.00 to 0.76; P = 0.050). Conclusions This study is the first to show that the GSTM1-null genotype, a common genetic variant, exerts significant additive interaction with HLA-DRB1 SE on the risk of ACPA positivity in RA. Since GSTM1 has known antioxidant functions, these data suggest that oxidative stress may be important in the development of RA-specific autoimmunity in genetically susceptible individuals
X-ray polarimetry reveals the magnetic field topology on sub-parsec scales in Tycho's supernova remnant
Supernova remnants are commonly considered to produce most of the Galactic
cosmic rays via diffusive shock acceleration. However, many questions about the
physical conditions at shock fronts, such as the magnetic-field morphology
close to the particle acceleration sites, remain open. Here we report the
detection of a localized polarization signal from some synchrotron X-ray
emitting regions of Tycho's supernova remnant made by the Imaging X-ray
Polarimetry Explorer. The derived polarization degree of the X-ray synchrotron
emission is 9+/-2% averaged over the whole remnant, and 12+/-2% at the rim,
higher than the 7-8% polarization value observed in the radio band. In the west
region the polarization degree is 23+/-4%. The X-ray polarization degree in
Tycho is higher than for Cassiopeia A, suggesting a more ordered magnetic-field
or a larger maximum turbulence scale. The measured tangential polarization
direction corresponds to a radial magnetic field, and is consistent with that
observed in the radio band. These results are compatible with the expectation
of turbulence produced by an anisotropic cascade of a radial magnetic-field
near the shock, where we derive a magnetic-field amplification factor of
3.4+/-0.3. The fact that this value is significantly smaller than those
expected from acceleration models is indicative of highly anisotropic
magnetic-field turbulence, or that the emitting electrons either favor regions
of lower turbulence, or accumulate close to where the magnetic-field
orientation is preferentially radially oriented due to hydrodynamical
instabilities.Comment: 31 pages, 7 figures, 3 tables. Accepted for publication in ApJ.
Revised versio
Magnetic structures and turbulence in SN 1006 revealed with imaging X-ray polarimetry
Young supernova remnants (SNRs) strongly modify surrounding magnetic fields,
which in turn play an essential role in accelerating cosmic rays (CRs). X-ray
polarization measurements probe magnetic field morphology and turbulence at the
immediate acceleration site. We report the X-ray polarization distribution in
the northeastern shell of SN1006 from a 1 Ms observation with the Imaging X-ray
Polarimetry Explorer (IXPE). We found an average polarization degree of
and an average polarization angle of
(measured on the plane of the sky from north to east). The X-ray polarization
angle distribution reveals that the magnetic fields immediately behind the
shock in the northeastern shell of SN 1006 are nearly parallel to the shock
normal or radially distributed, similar to that in the radio observations, and
consistent with the quasi-parallel CR acceleration scenario. The X-ray emission
is marginally more polarized than that in the radio band. The X-ray
polarization degree of SN 1006 is much larger than that in Cas A and Tycho,
together with the relatively tenuous and smooth ambient medium of the remnant,
favoring that CR-induced instabilities set the turbulence in SN 1006 and CR
acceleration is environment-dependent.Comment: 15 pages, 4 Figures, 2 Tables; accepted for publication in The
Astrophysical Journa
X-ray polarimetry of the accreting pulsar GX 301-2
The phase- and energy-resolved polarization measurements of accreting X-ray
pulsars (XRPs) allow us to test different theoretical models of their emission,
as well as to provide an avenue to determine the emission region geometry. We
present the results of the observations of the XRP GX 301-2 performed with the
Imaging X-ray Polarimetry Explorer (IXPE). GX 301-2 is a persistent XRP with
one of the longest known spin periods of ~680 s. A massive hyper-giant
companion star Wray 977 supplies mass to the neutron star via powerful stellar
winds. We do not detect significant polarization in the phase-averaged data
using spectro-polarimetric analysis, with the upper limit on the polarization
degree (PD) of 2.3% (99% confidence level). Using the phase-resolved
spectro-polarimetric analysis we get a significant detection of polarization
(above 99% c.l.) in two out of nine phase bins and marginal detection in three
bins, with a PD ranging between ~3% and ~10%, and a polarization angle varying
in a very wide range from ~0 deg to ~160 deg. Using the rotating vector model
we obtain constraints on the pulsar geometry using both phase-binned and
unbinned analysis getting excellent agreement. Finally, we discuss possible
reasons for a low observed polarization in GX 301-2.Comment: 10 pages, 10 figures, submitted to A&
A polarimetrically oriented X-ray stare at the accreting pulsar EXO 2030+375
Accreting X-ray pulsars (XRPs) are presumably ideal targets for polarization
measurements, as their high magnetic field strength is expected to polarize the
emission up to a polarization degree of ~80%. However, such expectations are
being challenged by recent observations of XRPs with the Imaging X-ray
Polarimeter Explorer (IXPE). Here we report on the results of yet another XRP,
EXO 2030+375, observed with IXPE and contemporarily monitored with Insight-HXMT
and SRG/ART-XC. In line with recent results obtained with IXPE for similar
sources, analysis of the EXO 2030+375 data returns a low polarization degree of
0%-3% in the phase-averaged study and variation in the range 2%-7% in the
phase-resolved study. Using the rotating vector model we constrain the geometry
of the system and obtain a value for the magnetic obliquity of ~.
Considering also the estimated pulsar inclination of ~, this
indicates that the magnetic axis swings close to the observer line of sight.
Our joint polarimetric, spectral and timing analysis hint to a complex
accreting geometry where magnetic multipoles with asymmetric topology and
gravitational light bending significantly affect the observed source behavior.Comment: A&A accepted. Proofs versio
X-ray pulsar GRO J100857 as an orthogonal rotator
X-ray polarimetry is a unique way to probe geometrical configuration of
highly-magnetized accreting neutron stars (X-ray pulsars). GRO J100857 is
the first transient X-ray pulsar observed at two different flux levels by the
Imaging X-ray Polarimetry Explorer (IXPE) during its outburst in November 2022.
The polarization properties were found to be independent of the source
luminosity, with the polarization degree varying between non-detection to about
15% over the pulse phase. Fitting the phase-resolved spectro-polarimetric data
with the rotating vector model allowed us to estimate the pulsar inclination
(130 deg, which is in good agreement with the orbital inclination), the
position angle (75 deg) of the pulsar spin axis, and the magnetic obliquity (74
deg). This makes GRO J100857 the first confidently identified X-ray pulsar
as a nearly orthogonal rotator. The results are discussed in the context of the
neutron star atmosphere models and theories of pulsars' axis alignment.Comment: 11 pages, 7 figures, submitted to A&A. arXiv admin note: text overlap
with arXiv:2209.0244
The first X-ray polarimetric observation of the black hole binary LMC X-1
We report on an X-ray polarimetric observation of the high-mass X-ray binary
LMC X-1 in the high/soft state, obtained by the Imaging X-ray Polarimetry
Explorer (IXPE) in October 2022. The measured polarization is below the minimum
detectable polarization of 1.1 per cent (at the 99 per cent confidence level).
Simultaneously, the source was observed with the NICER, NuSTAR and SRG/ART-XC
instruments, which enabled spectral decomposition into a dominant thermal
component and a Comptonized one. The low 2-8 keV polarization of the source did
not allow for strong constraints on the black-hole spin and inclination of the
accretion disc. However, if the orbital inclination of about 36 degrees is
assumed, then the upper limit is consistent with predictions for pure thermal
emission from geometrically thin and optically thick discs. Assuming the
polarization degree of the Comptonization component to be 0, 4, or 10 per cent,
and oriented perpendicular to the polarization of the disc emission (in turn
assumed to be perpendicular to the large scale ionization cone orientation
detected in the optical band), an upper limit to the polarization of the disc
emission of 1.0, 0.9 or 0.9 per cent, respectively, is found (at the 99 per
cent confidence level).Comment: 12 pages, 9 figures, 4 tables. Accepted for publication in MNRA
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